There are many classes of compounds known for treatment of psychotic disorders. For example, current therapeutic treatments for psychoses use compounds classifiable as tricyclic-type phenothiazine-thioxanthenes, as phenylbutylpiperidines and also as alkaloids. An example of a piperazine-substituted tricyclic compound of current use in psychotic treatment therapy is fluphenazine [A. F. Gilman et al, The Pharmacological Basis of Therapeutics, 7th End., p. 403, MacMillan (1985)].
Tricyclic compounds have been investigated for various CNS uses. For example, Belgian Patent No. 706,262 describes a class of diphenylenemethane amine and amide derivatives mentioned for use as anticonvulsants, as well as for antidepressive, antiinflammatory and analgesic uses, and mentions in particular the compound 2-[fluorene-9-yl)amino]acetamide. U.S. Pat. No. 3,821,249 describes a series of dibenzothiazepin derivatives asserted to possess psychostimulant, antidepressive, analgesic, antitussive, antihistaminic and gastric anti-secretory properties, such series including certain specific 7-[dibenzo(a,d)cycloheptadien-5-yl]aminoheptanoic acid derivatives and certain specific 7-[chlorodibenzo(b,e)thiepin-11-yl]aminoheptanoic acid derivatives.
It has been shown that the sensitivity of central neurons to hypoxia and ischemia can be reduced by either blockage of synaptic transmission or by the specific antagonism of postsynaptic glutamate receptors [see S. M. Rothman et al, Annals of Neurology, 19(2), 105-111 (1986)]. Glutamate is characterized as a broad spectrum agonist having activity at three neuronal excitatory amino acid receptor sites. These receptor sites are named after the amino acids which selectively excite them, namely: Kainate (KA), N-methyl-D-aspartate (NMDA or NMA) and quisqualate (QUIS).
It is known that compounds of various structures, such aminophosphonovalerate derivatives and piperidine dicarboxylate derivatives, may act as competitive antagonists at the NMDA receptor. Certain piperidineethanol derivatives, such as ifenprodil and 1-(4-chlorophenyl)-2-[1-(4-fluorophenyl)piperidinyl]ethanol, which are known anti-ischemic agents, have been found to be non-competitive NMDA receptor antagonist [C. Carter et al, J. Pharm Exp. Ther., 247(3), 1222-1232 (1988)].
Other families of bridged bicyclic amine compounds have been investigated for CNS-related purposes. For example, certain primary and secondary benzobicyclo-[2.2.2]octeneamine compounds have been studied as uptake inhibitors of central catecholamines [R. M. Bartholow et al, J. Pharm. Exp. Ther., 202(3), 532-543 (1977)]. Also, U.S. Pat. No. 4,801,753 describes a family of 4-aminobenzo(b)bicyclo[3.3.1]nonene derivatives an antidepressant agents.